Professor of Obstetrics and Gynecology (Reproductive Endocrinology and Infertility) at Stanford University Medical Center

Obstetrics & Gynecology - Reproductive Endocrinology & Infertility

Bio

Bio

Lynn Marie Westphal, M.D., FACOG, graduated summa cum laude from Lawrence University, earned her M.D. degree at Stanford University, and did her residency training in obstetrics and gynecology at UCLA and Stanford University. She did a fellowship in molecular biology at Stanford University and completed her fellowship in Reproductive Endocrinology and Infertility (REI) at UCSF.

Dr. Westphal joined the full-time faculty at Stanford University in 1998 and is an Associate Professor in the Department of Gynecology and Obstetrics, Director of the Fertility Preservation Program, Director of the Third Party Reproduction Program, and Director of the REI Fellowship. Her interest in fertility preservation for cancer survivors led her to set up one of the first oocyte cryopreservation programs in the country. She has held numerous national leadership positions and was the President of the Fertility Preservation Special Interest Group of the American Society of Reproductive Medicine from 2008-2009. She was the Director of Women’s Health at Stanford from 2005-2012. In 2012, she co-founded the Stanford Center for Health Research on Women and Sex Differences in Medicine (WSDM) and served as co-director of the program for two years.

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Research & Scholarship

Current Research and Scholarly Interests

Infertility, fertility preservation, oocyte cryopreservation

Clinical Trials

Effect of Healing Touch on the Experience of Women Undergoing Treatment for Breast CancerNot Recruiting

To learn what effect, if any, Healing Touch (a gentle, non-invasive form of energy work that
promotes relaxation and can help manage the side effects of chemotherapy and radiation), has
on physical symptoms, mood, and qualify of life for women undergoing treatment for breast
cancer.

Given the potential of semi-quantitative pregnancy tests as part of assisted fertility care,
the investigators would like to document the feasibility and acceptability of a
semi-quantitative pregnancy test as an adjunct to or replacement of current monitoring
protocols to offer women and health care providers a new choice of diagnostic tools to
confirm early pregnancy. The pilot will help us to better understand how this tool
complements existing monitoring protocols. If a suitable addition or replacement to repeat
blood draws for serum hCG assessment, the SQPT could also contribute to efforts to make
assisted fertility treatments more patient-friendly. This study seeks to test this
innovation by asking women assigned to perform a Quanti5 Multilevel hCG Pregnancy Test
(Athenium Pharmaceuticals, LLC, Nashville, TN) at home on a weekly basis for up to 4 weeks
after egg retrieval/embryo transfer or intrauterine insemination.
The investigators hypothesize that the test, which can be used at home by women, will
provide confirmation of the presence of a pregnancy compared with standard serum hCG testing
because 1) it has sensitivity and specificity that correlates well with serum testing, and
2) it can be used at home and thus earlier to determine presence of hCG.

Abstract

To study pregnancy outcomes between South Asian and Caucasian women undergoing frozen blastocyst transfer cycles.Retrospective cohort study.Not applicable.Caucasian and South Asian patients undergoing frozen blastocyst transfer between January 2011 and December 2014.Not applicable.Live birth rate.A total of 196 Caucasian and 117 South Asian women were included in our study. Indians were on average 2.2 years younger than Caucasian women (34.9 vs. 37.1 years), and were more likely to be nulliparous (59% vs. 43%). All other baseline characteristics were similar. In women undergoing their first frozen ET cycle, implantation rate (49% vs. 47%), clinical pregnancy rate (PR; 54% vs. 49%), and live birth rate (43% vs. 43%) were similar between South Asians and Caucasians, respectively. In patients who underwent a prior fresh blastocyst transfer, the live birth rate was significantly lower in South Asian versus Caucasian women (21% vs. 37%).Our data demonstrate that IVF outcomes are better in frozen versus fresh cycles among South Asian women. The IVF clinics may wish to consider these findings when counseling South Asian patients about the timing of ET.

Abstract

Recurrent pregnancy loss (RPL), defined as two or more consecutive miscarriages, is attributable to multiple causes. However, in 50% of cases no known cause is found. Although endometritis is a known cause of miscarriage, other inflammatory processes may play a role in idiopathic, recurrent loss. The fetoplacental unit evades rejection by the maternal immune system by poorly understood mechanisms. Despite this seemingly immune-privileged state for the fetus, human implantation requires inflammatory mediators for attachment and implantation. This review describes how the immune system must simultaneously permit and restrict trophoblastic invasion for healthy implantation and maintenance of pregnancy. Included in this review is a detailed description of the immune milieu in the decidua and abnormalities that are associated with RPL. Finally, autoimmune states associated with RPL and their treatment in an obstetrical setting are reviewed.

Abstract

Researchers have hypothesized that an imbalance of immune cells in the uterine decidua and a dysfunction in cytokines they produce may contribute to recurrent pregnancy loss (RPL). The objective of this study was to determine if IL-22, IL-23 and IL-17 are expressed abnormally in the decidua of patients with RPL compared to those women with a normal pregnancy. We also sought to confirm that uterine natural killer (uNK) cells are lower in the decidua of patients with RPL, as well as identify IL-22 expression by uNK cells.After meeting strict inclusion criteria, maternal decidua of nine patients with unexplained RPL and a confirmed euploid fetal loss, and 11 gestational age-matched patients undergoing elective pregnancy termination were included in our analysis. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression, Western blot was performed to quantify protein expression and immunohistochemistry (IHC) was performed to identify IL-22 and uNK cells.We found that women with unexplained RPL and a euploid fetal loss had significantly less gene and protein expression of IL-22 in the decidua. Additionally, we found that IL-22 is primarily expressed by uNK cells in the decidua.In conclusion, our results suggest that lower levels of IL-22 in the uterine decidua in patients with unexplained RPL may contribute to a disruption of decidual homeostasis and ultimately lead to early pregnancy loss.

Abstract

A map of human embryo development that combines imaging, molecular, genetic and epigenetic data for comparisons to other species and across pathologies would be greatly beneficial for basic science and clinical applications. Here, we compared mRNA and protein expression of key mediators of DNA methylation and histone modifications between mouse and human embryos, embryos from fertile/infertile couples, and following growth factor supplementation. We observed that individual mouse and human embryos are characterized by similarities and distinct differences in DNA methylation and histone modification patterns especially at the single-cell level. In particular, while mouse embryos first exhibited sub-compartmentalization of different histone modifications between blastomeres at the morula stage and cell sub-populations in blastocysts, differential histone modification expression was detected between blastomeres earlier in human embryos at the four- to eight-cell stage. Likewise, differences in epigenetic mediator expression were also observed between embryos from fertile and infertile couples, which were largely equalized in response to growth factor supplementation, suggesting that select growth factors might prevent alterations in epigenetic profiles during prolonged embryo culture. Finally, we determined that reduced expression via morpholino technologies of a single histone-modifying enzyme, Rps6ka4/Msk2, resulted in cleavage-stage arrest as assessed by time-lapse imaging and was associated with aneuploidy generation. Taken together, data document differences in epigenetic patterns between species with implications for fertility and suggest functional roles for individual epigenetic factors during pre-implantation development.

Abstract

Hyperandrogenic conditions in women are associated with increased rates of miscarriage. However, the specific role of maternal testosterone in early pregnancy and its association with pregnancy outcome is unknown. The purpose of this study was to compare serum testosterone levels during early pregnancy in women with and without polycystic ovary syndrome (PCOS) who either had successful pregnancies or miscarried.We collected serum samples from women attending a university-based fertility centre at the time of their first positive serum beta human chorionic gonadotropin pregnancy test. The samples were subsequently assayed for total testosterone level. We used logistical regression modelling to control for PCOS diagnosis, BMI, and age.Total testosterone levels were available for 346 pregnancies, including 286 successful pregnancies and 78 first trimester miscarriages. We found no difference in total testosterone levels between women who subsequently had an ongoing pregnancy (mean concentration 3.6 ± 2.6 nmol/L) and women with a miscarriage (mean 3.6 ± 2.4 nmol/L). Using the Rotterdam criteria to identify women with PCOS, we also found no differences in serum testosterone between women who had ongoing pregnancies or miscarriages, either with PCOS (P = 0.176) or without PCOS (P = 0.561).Our findings show that early pregnancy testosterone levels do not predict pregnancy outcome, and they call into question the role of testosterone in causing miscarriage in populations of women with PCOS. Further research is needed to elucidate the normal progression of testosterone levels during pregnancy and to investigate further the relationship between PCOS and miscarriage.

Abstract

An estimated 7 million American couples per year seek infertility care in the United States. A male factor contributes to 50% of cases but it is unclear what proportion of infertile couples undergoes male evaluation.We analyzed data from cycles 5 to 7 of the National Survey of Family Growth performed by the Centers for Disease Control to determine the frequency of a male infertility evaluation, and associated reproductive and demographic factors.A total of 25,846 women and 11,067 men were surveyed. Male evaluation was not completed in 18% of couples when the male partner was asked vs 27% when female partners were asked. This corresponds to approximately 370,000 to 860,000 men in the population who were not evaluated at the time of infertility evaluation. Longer infertility duration and white race were associated with increased odds of male infertility evaluation. The male and female samples showed no change in the receipt of male examination with time.Many men from infertile couples do not undergo male evaluation in the United States. Given the potential implications to reproductive goals and male health, further examination of this pattern is warranted.

Abstract

The role of stress in reproduction, particularly during treatment for infertility, has been of considerable interest; however, few studies have objectively measured stress and anxiety over the course of the IVF cycle or compared the experience of first-time and repeat patients.This prospective cohort pilot study enrolled 44 women undergoing IVF at a university-based clinic to complete the State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS) and Infertility Self-Efficacy Scale (ISES) at three time points prior to ovarian stimulation (T1), one day prior to oocyte retrieval (T2), and 5-7 days post embryo transfer (T3).Mean STAI State scores were significantly elevated at all three time points (p<0.01). STAI State and PSS mean values did not change over time and did not differ in first-time vs. repeat patients. Self-efficacy (ISES) scores declined over time, with a greater decline for repeat patients. Of the 36 women who completed a cycle, 15 achieved clinical pregnancy. Using logistic regression modeling, all scores at T2 were correlated with pregnancy outcome with lower scores on the STAI State and PSS and higher scores on the ISES associated with higher pregnancy rates.Stress and anxiety levels remained elevated across all cycles. Women with lower stress and anxiety levels on the day prior to oocyte retrieval had a higher pregnancy rate. These results emphasize the need to investigate stress reduction modalities throughout the IVF cycle.

Abstract

Preimplantation genetic diagnosis (PGD) is an increasingly common adjunct to IVF. The information gained from PGD may be used to reduce the incidence of chromosomally abnormal pregnancies and augment the current selection process of embryos. As such, patients may choose to utilize PGD in either fresh or cryopreserved IVF cycles. It is a common practice to cryopreserve excess embryos at the blastocyst stage. In these cases, trophectoderm biopsy is the only technique available for PGD. This articles reports this study centre's experience with trophectoderm biopsies of cryopreserved blastocysts in 12 patients who underwent 13 cycles of PGD. The implantation rate per embryo transferred was 46% and the ongoing pregnancy rate per embryo transfer was 63%. The results from this case series demonstrate that trophectoderm biopsy on cryopreserved blastocysts to perform PGD is logistically feasible. In addition, the rate of implantation and ongoing pregnancy were maintained within a reasonable range to justify the procedure. Preimplantation genetic diagnosis (PGD) is an increasingly common adjunct to IVF and is used to evaluate the genetic makeup of the embryo prior to transfer of the embryo into the uterus. The information gained from PGD may be used to identify single-gene disorders that result in genetic disease, reduce the incidence of chromosomally abnormal pregnancies and/or augment the selection process of embryos to be transferred. In order to perform PGD, a biopsy of the embryo is the performed and cells are removed for testing. PGD may be performed in either fresh or frozen (cryopreserved) IVF cycles. Patients who have cryopreserved embryos remaining in storage from a previous fresh cycle may wish to have these embryos tested with PGD. Many embryos are frozen on day 5 of development, referred to as the blastocyst stage. At this stage of development, embryo biopsy is performed via a technique known as 'trophectoderm biopsy', in which 1-3 of the cells destined to become the placenta are removed from the embryo for chromosomal testing. We report our experience with trophectoderm biopsy of frozen blastocysts in 12 patients who underwent 13 cycles of PGD. The implantation rate per embryo transferred was 46% and the ongoing pregnancy rate per embryo transfer was 63%. The results from this case series demonstrate that trophectoderm biopsy on cryopreserved blastocysts to perform PGD is logistically feasible. In addition, the rate of implantation and ongoing pregnancy were maintained within a reasonable range to justify the procedure.

Abstract

Recurrent pregnancy loss (RPL) occurs in ?5% of women. However, the etiology is still poorly understood. Defects in decidualization of the endometrium during early pregnancy contribute to several pregnancy complications, such as pre-eclampsia and intrauterine growth restriction (IUGR), and are believed to be important in the pathogenesis of idiopathic RPL. We performed microarray analysis to identify gene expression alterations in the deciduas of idiopathic RPL patients. Control patients had one antecedent term delivery, but were undergoing dilation and curettage for current aneuploid miscarriage. Gene expression differences were evaluated using both pathway and gene ontology (GO) analysis. Selected genes were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A total of 155 genes were found to be significantly dysregulated in the deciduas of RPL patients (>2-fold change, P < 0.05), with 22 genes up-regulated and 133 genes down-regulated. GO analysis linked a large percentage of genes to discrete biological functions, including immune response (23%), cell signaling (18%) and cell invasion (17.1%), and pathway analysis revealed consistent changes in both the interleukin 1 (IL-1) and IL-8 pathways. All genes in the IL-8 pathway were up-regulated while genes in the IL-1 pathway were down-regulated. Although both pathways can promote inflammation, IL-1 pathway activity is important for normal implantation. Additionally, genes known to be critical for degradation of the extracellular matrix, including matrix metalloproteinase 26 and serine peptidase inhibitor Kazal-type 1, were also highly up-regulated. In this first microarray approach to decidual gene expression in RPL patients, our data suggest that dysregulation of genes associated with cell invasion and immunity may contribute significantly to idiopathic recurrent miscarriage.

Abstract

Young women diagnosed with breast cancer typically face systemic treatments that may delay childbearing or permanently impair their fertility. These concerns add to the stress experienced by young cancer survivors. Timely counseling and providing fertility preservation through cryopreservation of eggs or embryos have become an important quality of life issue. We analyzed the impact of fertility preservation procedures on the initiation of treatment for breast cancer and discuss critical aspects of the process.

Abstract

This prospective cohort study of infertility patients compared testosterone concentrations in early pregnancy in infertility patients who conceived naturally or after treatment. Although all groups demonstrated some increase in pregnancy testosterone from baseline concentrations, subjects who conceived following ovulation induction showed a significantly increased rise in testosterone as compared with controls (P<0.01).

Abstract

To examine early pregnancy (EP) testosterone (T) after ovarian stimulation and its effect on singleton pregnancy outcomes.Prospective cohort study.University-based tertiary care center.Subfertile women who conceived with or without fertility treatment.Ovarian stimulation for assisted reproduction, collection of serum total T levels in early pregnancy, and pregnancy follow-up.Rate of preterm delivery, low birth weight (LBW) (<2,500 g), and hypertensive disorders of pregnancy.EP serum samples were measured from 266 singleton pregnancies. The mean T level among spontaneous conceptions was 74.90 ng/dL (SD 48.35 ng/dL); 103 ng/mL was the 90th percentile. Mean EP T was increased among patients who underwent ovarian stimulation compared with nonstimulated control subjects. In patients undergoing IVF, T levels in EP were linearly correlated with the number of oocytes retrieved. When pregnancy outcomes in women with normal T were compared with women with elevated T (>90th percentile), we did not see an increased risk for preterm delivery, hypertensive disorders of pregnancy, LBW infants, or cesarean delivery (odds ratio ratios 1.43, 0.38, 1.39, and 0.85, respectively).Elevations in EP T are associated with ovarian stimulation but do not appear to be associated with adverse pregnancy outcome. Further investigation to determine the etiology of increased maternal and neonatal morbidity among subfertile women is warranted.

Abstract

Advances in cancer treatment have allowed women to live longer, fuller lives. However, gonadotoxic therapies used to effect cancer 'cures' often significantly impair a woman's reproductive potential. Thus, in accordance with improved survival rates, there is an increase in demand for fertility preservation. Initially, fertility preservation was limited to embryo cryopreservation; therefore, the number of patients enrolling was relatively low. Recently, substantial improvements have increased available options, specifically oocyte cryopreservation, thereby expanding and altering the make-up of the patient population undergoing treatment for fertility preservation. Patient diversity requires the treating physician(s) to be cognizant of issues specific to cancer type and stage. Furthermore, patients often have comorbidities which must be attended to and addressed. Although not all patients will be candidates for, or will elect to pursue, fertility preservation, all should receive counselling regarding their options. This practice will ensure that the reproductive rights of those patients facing impending sterility are maintained. Here, fertility preservation protocols, practices and special considerations, categorized by most frequently encountered cancer types, are reviewed to guide reproductive endocrinologists in the management of fertility preservation in such patients. The formation of a multidisciplinary patient-structured team will ensure a successful, yet safe, fertility-preservation outcome. Advances in cancer treatment have allowed women to live longer, fuller lives. However, therapies used to treat cancer often significantly impair a woman's future ability to have children by damaging her eggs or removing key reproductive organs. Given that women are now often living well beyond their cancer diagnosis and treatment, there is an increased interest in preserving reproductive potential. Thus, the field of fertility preservation has been developed and continues to grow. Initially, fertility preservation was limited to freezing embryos formed by combining an egg with spermatozoa. One drawback of this approach is that it requires both female and male contributions. Recently, substantial improvements have expanded the available options, including freezing unfertilized eggs, affording female patients fertility preservation without a requisite male partner or donor. Cancer patients vary widely, requiring the treating physician(s) to be cognizant of issues specific to individual cancer types and extent of disease. Furthermore, cancer patients often have co-existing medical conditions which must be attended to and addressed. Although not all patients will be candidates for, or elect to pursue, fertility preservation, all should receive counselling regarding their options. This will ensure that the reproductive rights of cancer patients facing impending sterility are maintained. Here, we review fertility preservation protocols, practices and special considerations, categorized by the most commonly encountered cancer types, to guide physicians in the management of fertility preservation in such patients. We advocate the formation of a multidisciplinary patient-structured team to ensure a successful and safe fertility-preservation outcome.

Abstract

BACKGROUND IVF, using donor oocytes, has become increasingly common. The donation procedure carries psychiatric risks, including depression, anxiety and rarely, psychosis, and this risk increases when there is a past history of psychiatric illness. We report on the psychiatric status, at intake assessment, of a group of candidate oocyte donors. METHODS The authors reviewed clinical records of 63 women continuously presenting to a University medical center for psychiatric evaluation as part of the screening process for oocyte donation. A board certified psychiatrist administered a structured clinical interview to candidate donors, and self-report measures were obtained from 28 women. RESULTS There was a significant discrepancy between psychiatric history of depression and current mood status, as measured by both clinical interview and psychometric self-report data. Nearly one-quarter of candidate donors (22%) reported a history of major depressive disorder; however, all candidate donors denied current mood disturbance on clinical interview, and mean Beck depression inventory and profile of mood states scores were lower than expected compared with psychometric norms (P < 0.0005), epidemiological data and the recurrent nature of depressive disorders. CONCLUSIONS Candidate donors may minimize psychiatric symptoms. Given the potential for ovarian stimulation protocols to induce or exacerbate mood symptoms, and the moderate heritability of mood disorders, careful evaluation of candidate donor affective disorder history is recommended. This evaluation should focus on sensitivity to mood destabilization during times of hormonal change. Measures that examine whether a candidate donor may have a tendency to present herself in an overly favorable manner, and/or a tendency to minimize symptoms, are recommended.

Abstract

To examine the rate of aneuploidy in missed abortions in patients who conceived after FSH ovarian stimulation compared with women who conceived in a natural cycle.Retrospective cohort.Academic reproductive endocrinology and infertility center.Women with karyotyping of products of conception (POC) from a missed abortion from January 1999 through August 2007. The rate of aneuploidy was compared between patients with a history of infertility who conceived naturally and patients with a history of infertility who conceived with FSH treatment.Ovarian stimulation with FSH, intrauterine insemination, and in vitro fertilization; genetic testing of POC after dilation and curettage.Embryonic karyotype.A total of 229 pregnancies met inclusion criteria, and of these, 64% had an abnormal karyotype. The rate of aneuploidy was 63% in the study group and 70% in the control group. This difference was not statistically significant.The incidence of embryonic aneuploidy was not higher in pregnancies conceived with FSH stimulation compared with spontaneous conceptions in infertility patients. This suggests that exogenous FSH exposure does not increase the risk of aneuploidy.

Abstract

Background. Although the optimal outcome of assisted reproductive technology (ART) is a healthy singleton pregnancy, the rate of twin gestation from ART in women over the age of 35 is persistently high. Methods/Findings. We compared clinical pregnancy rates (PRs), ongoing pregnancy/live birth rates, and multiple gestation rates (MGRs) in 108 women who chose elective single blastocyst transfer (eSBT) to 415 women who chose elective double blastocyst transfer (eDBT) at a hospital-based IVF center. There was no significant difference in PR between eSBT and eDBT (57.4% versus 50.2%, P = 0.47) nor between eSBT and eDBT within each age group: <35, 35-37, 38-40, and >40. The risk of multiple gestations, however, was greatly increased between eSBT and eDBT (1.6 versus 32.4%, P < 0.00005), and this difference did not vary across age groups. Conclusion(s). Women undergoing eDBT are at uniformly high risk of multiple gestation regardless of age. eSBT appears to significantly lower the risk of multiple gestation without compromising PR.

Abstract

Day 2 embryo transfer has been suggested as a method to improve pregnancy rates in poor responders compared with day 3 transfer. Our prospective randomized controlled trial does not show a difference in outcomes based on day of embryo transfer.

Abstract

To determine the impact of infertility on female sexual function.A case-control study.Academic infertility and gynecology practices.One hundred nineteen women with infertility and 99 healthy female controls without infertility between the ages of 18 and 45 years were included in this study.Anonymous survey and Female Sexual Function Index.Female Sexual Function Index scores, frequency of sexual intercourse and masturbation, and sex-life satisfaction.Twenty-five percent of our control group had Female Sexual Function Index scores that put them at risk for sexual dysfunction (<26.55), whereas 40% of our patients with infertility met this criterion. Compared with the control group, the patients with infertility had significantly lower scores in the desire and arousal domains and lower frequency of intercourse and masturbation. The patients with infertility retrospectively reported a sex-life satisfaction score that was similar to that of the controls before their diagnosis, whereas their current sex-life satisfaction scores were significantly lower than those of the controls.Women with a diagnosis of infertility were found to be at higher risk for sexual dysfunction on the basis of their Female Sexual Function Index scores compared with women without infertility. The interaction of sexual function and infertility is complex and deserves further study.

Abstract

Cystic fibrosis (CF) is one of the most common genetic disorders that can often lead to chronic pulmonary disease. Patients with respiratory failure due to CF may achieve a good quality of life after lung transplant, and many will desire to have children.A 26-year-old, nulliparous female with CF and double lung transplant presented for fertility treatment. She was successfully treated with controlled ovarian hyperstimulation and gestational surrogacy.Controlled ovarian hyperstimulation and gestational surrogacy is a safe option for patients with lung transplant to have a genetic child.

Abstract

To determine the rate of embryonic chromosomal abnormalities, thrombophilias, and uterine anomalies in women over the age of 35 years with recurrent pregnancy loss (RPL).Retrospective cohort study.Academic reproductive endocrinology and infertility clinic.Women>or=35 years old with >or=3 first trimester miscarriages.None.Age, number of prior losses, cytogenetic testing of the products of conception (POC), uterine cavity evaluation, parental karyotype, TSH, and antiphospholipd antibody (APA) and thrombophilia testing. Aneuploidy in the POC in women with RPL was compared with sporadic miscarriages (or=35 years.Among 43 RPL patients, there were 50 miscarriages in which cytogenetic analysis was performed. In the RPL group, the incidence of chromosomal abnormalities in the POC was 78% (39 out of 50) compared with a 70% incidence (98 out of 140) in the sporadic losses. Thrombophilia results in the RPL patients were normal in 38 patients, four patients had APA syndrome, and one had protein C deficiency. Forty out of 43 had normal uterine cavities. Both TSH and parental karyotypes were normal in all of the patients tested. When the evaluation of RPL included karyotype of the POC, only 18% remained without explanation. However, without fetal cytogenetics, 80% of miscarriages would have been unexplained.In older patients with RPL, fetal chromosomal abnormalities are responsible for the majority of miscarriages. Other causes were present in only 20% of cases.

Abstract

Nearly 75% of in vitro fertilization (IVF) treatments do not result in live births and patients are largely guided by a generalized age-based prognostic stratification. We sought to provide personalized and validated prognosis by using available clinical and embryo data from prior, failed treatments to predict live birth probabilities in the subsequent treatment. We generated a boosted tree model, IVFBT, by training it with IVF outcomes data from 1,676 first cycles (C1s) from 2003-2006, followed by external validation with 634 cycles from 2007-2008, respectively. We tested whether this model could predict the probability of having a live birth in the subsequent treatment (C2). By using nondeterministic methods to identify prognostic factors and their relative nonredundant contribution, we generated a prediction model, IVF(BT), that was superior to the age-based control by providing over 1,000-fold improvement to fit new data (p<0.05), and increased discrimination by receiver-operative characteristic analysis (area-under-the-curve, 0.80 vs. 0.68 for C1, 0.68 vs. 0.58 for C2). IVFBT provided predictions that were more accurate for approximately 83% of C1 and approximately 60% of C2 cycles that were out of the range predicted by age. Over half of those patients were reclassified to have higher live birth probabilities. We showed that data from a prior cycle could be used effectively to provide personalized and validated live birth probabilities in a subsequent cycle. Our approach may be replicated and further validated in other IVF clinics.

Abstract

Approximately 20% of oocytes are classified as immature and discarded following intracytoplasmic sperm injection (ICSI) procedures. These oocytes are obtained from gonadotropin-stimulated patients, and are routinely removed from the cumulus cells which normally would mature the oocytes. Given the ready access to these human oocytes, they represent a potential resource for both clinical and basic science application. However culture conditions for the maturation of cumulus-free oocytes have not been optimized. We aimed to improve maturation conditions for cumulus-free oocytes via culture with ovarian paracrine/autocrine factors identified by single cell analysis.Immature human oocytes were matured in vitro via supplementation with ovarian paracrine/autocrine factors that were selected based on expression of ligands in the cumulus cells and their corresponding receptors in oocytes. Matured oocytes were artificially activated to assess developmental competence. Gene expression profiles of parthenotes were compared to IVF/ICSI embryos at morula and blastocyst stages. Following incubation in medium supplemented with ovarian factors (BDNF, IGF-I, estradiol, GDNF, FGF2 and leptin), a greater percentage of oocytes demonstrated nuclear maturation and subsequently, underwent parthenogenesis relative to control. Similarly, cytoplasmic maturation was also improved as indicated by development to blastocyst stage. Parthenogenic blastocysts exhibited mRNA expression profiles similar to those of blastocysts obtained after IVF/ICSI with the exception for MKLP2 and PEG1.Human cumulus-free oocytes from hormone-stimulated cycles are capable of developing to blastocysts when cultured with ovarian factor supplementation. Our improved IVM culture conditions may be used for obtaining mature oocytes for clinical purposes and/or for derivation of embryonic stem cells following parthenogenesis or nuclear transfer.

Abstract

To estimate the effect of ethnicity on in vitro fertilization (IVF) outcomes after blastocyst transfer.We conducted a review of fresh blastocyst transfer IVF cycles from January 1, 2005, to December 31, 2006. Data collection included demographic information, infertility history, treatment protocol details, and treatment outcomes. Statistics were performed using the Student t test and chi2 test. To establish the independent contribution of Asian ethnicity, a multivariable logistic regression analysis was performed.We reviewed 180 blastocyst transfer cycles among white (62%) and Asian (38%) women. The groups were similar in most baseline characteristics. Asian women, however, had a lower body mass index (22.6 compared with 24.2, P=.02), were more likely to be nulligravid (53% compared with 35%, P=.03), and were more likely to have had at least one prior IVF cycle (37% compared with 20%, P=.02) The groups were similar in treatment characteristics, number of oocytes retrieved, fertilization rate, and number of blastocysts transferred. However, Asian women had a thicker endometrial lining (10.9 compared with 10.2, P=.02). Despite these similarities, Asian women had a lower implantation rate (28% compared with 45%, P=.01), clinical pregnancy rate (43% compared with 59%, P=.03), and live birthrate (31% compared with 48%, P=.02). In multivariable analysis, the decreased live birthrate among Asian women persisted (adjusted odds ratio 0.48, 95% confidence interval 0.24-0.96, P=.04).When compared with white women, Asian women have lower clinical pregnancy and live birthrates after blastocyst transfer.

Abstract

To evaluate controlled ovarian hyperstimulation (COH) in women with cancer compared with healthy women.A retrospective cohort study.Academic assisted reproductive technology (ART) program.Fifty women undergoing oocyte retrieval before cancer treatment and 50 age-matched controls.None.Number of oocytes and matured oocytes retrieved, number of fertilized oocytes, days of stimulation, dose of gonadotropins.There were no significant differences in the number of oocytes retrieved (13 vs. 11.5), the number of matured oocytes retrieved (9.7 vs. 9.6), and the number of oocytes fertilized (7.4 vs. 6.8). However, the patients with cancer had a longer duration of stimulation (10.5 vs. 9.0 days) and higher total dose of gonadotropins (4,174 IU vs. 3,416 IU).In our study, reasonable ovarian response was achieved by women with cancer with increased doses of gonadotropins and a longer duration of stimulation.

Abstract

Protecting future childbearing motivates young women with breast cancer to seek oocyte or embryo cryopreservation. Concerns about delays in cancer treatment may influence patients and practitioners considering these procedures. In this study, we compared timing of chemotherapy in women who underwent ovarian stimulation/oocyte retrieval (OR) and embryo cryopreservation with those who did not.Eighty-two women younger than 40 years of age, who received adjuvant chemotherapy for breast cancer, were retrospectively identified. Nineteen underwent OR and 63 did not (CON). The timing of OR, surgery, and chemotherapy were compared with the time intervals between diagnosis and treatments in the CON group.The mean ages of women were 33.7 years (OR group) and 35.2 years (CON group); 84.2% of OR and 25.4% of CON were nulliparous. The median time from initial diagnosis to reproductive endocrinology consultation was 30.1 days (range 4 to 133 days) and from referral to OR was 32 days (range 13 to 66 days). The median times from initial diagnosis to chemotherapy in OR versus CON groups were 71 days (range 45 to 161 days) and 67 days (range 27 to 144 days), respectively, p < 0.27. The median time interval from definitive operation to chemotherapy was similar in the two groups: 30 days (OR; range 14 to 100 days) and 29 days (CON; range 12 to 120 days), p < 0.79.Fertility preservation is an important component of quality of life for young women with breast cancer. The time investment required for OR and cryopreservation is manageable and does not significantly prolong the time interval from diagnosis to start of adjuvant chemotherapy.

Abstract

Disease prevalence and response to medical therapy may differ among patients of diverse ethnicities. Poor outcomes with in vitro fertilization (IVF) treatment have been previously shown in Indian women compared to Caucasian women, and some evidence suggests that poor embryo quality may be a cause for the discrepancy. In our center, only patients with the highest quality cleavage stage embryos are considered eligible for extending embryo culture to the blastocyst stage. We compared live birth rates (LBR) between Indian and Caucasian women after blastocyst transfer to investigate whether differences in IVF outcomes between these ethnicities would persist in patients who transferred similar quality embryos.In this retrospective cohort analysis, we compared IVF outcome between 145 Caucasians and 80 Indians who had a blastocyst transfer between January 1, 2005 and June 31, 2007 in our university center. Indians were younger than Caucasians by 2.7 years (34.03 vs. 36.71, P = 0.03), were more likely to have an agonist down regulation protocol (68% vs. 43%, P<0.01), and were more likely to have polycystic ovarian syndrome (PCOS), although not significant, (24% vs. 14%, P = 0.06). Sixty eight percent of Indian patients had the highest quality embryos (4AB blastocyst or better) transferred compared to 71% of the Caucasians (P = 0.2). LBR was significantly lower in the Indians compared to the Caucasians (24% vs. 41%, P<0.01) with an odds ratio of 0.63, (95%CI 0.46-0.86). Controlling for age, stimulation protocol and PCOS showed persistently lower LBR with an adjusted odds ratio of 0.56, (95%CI 0.40-0.79) in the multivariate analysis.Despite younger age and similar embryo quality, Indians had a significantly lower LBR than Caucasians. In this preliminary study, poor prognosis after IVF for Indian ethnicity persisted despite limiting analysis to patients with high quality embryos transferred. Further investigation into explanations for ethnic differences in reproduction is needed.

Abstract

A review of 950 patients was performed to investigate the impact of selective serotonin reuptake inhibitors (SSRIs) on in vitro fertilization outcome. The 41 patients (4.3%) taking an SSRI had a higher cycle cancellation rate but no statistically significant difference in pregnancy rate and live birth rate per cycle started.

Abstract

To report a case of successful pregnancy after trophectoderm biopsy and fluorescence in situ hybridization (FISH) revealed a tetraploid karyotype.Case report.A university medical center.An infertility patient desiring trophectoderm biopsy on frozen blastocysts to facilitate preimplantation genetic screening.Frozen blastocysts were thawed on the evening before transfer. Trophectoderm biopsy was performed the following morning. FISH results were available the same day, and two embryos with tetraploid results were transferred.Chorionic villus sample (CVS) and newborn exam.Normal diploid CVS result and a healthy male infant.Although multiple cells can be analyzed using trophectoderm biopsy, abnormalities in the trophectoderm may not be present in the inner cell mass.

Abstract

To evaluate the pregnancy rate, ovarian responsiveness, and endometrial thickness in infertility patients with a history of methotrexate exposure who subsequently underwent controlled ovarian stimulation.Retrospective cohort study.University reproductive endocrinology and infertility program.Forty-eight women with infertility undergoing ovarian stimulation after receiving methotrexate treatment for ectopic gestation.Methotrexate administration and controlled ovarian stimulation.Pregnancy rate, cycle day 3 FSH levels, number of oocytes retrieved, and endometrial thickness.The cumulative intrauterine pregnancy rate achieved with controlled ovarian stimulation at 2 years after methotrexate exposure was 43%, with a mean time to conceive of 181 days. Thirty-five patients with similar fertility treatments pre- and post-methotrexate were identified. Within this group, when an IVF cycle occurred within 180 days of methotrexate exposure, a significant decline in oocytes retrieved was observed. Cycles performed later than 180 days after methotrexate exposure did not exhibit a decrease in oocyte production. Endometrial development was similar at all time points examined.These findings suggest a time-limited and reversible impact of methotrexate on oocyte yield. If confirmed by larger clinical series and/or animal data, these results may impact the management of ectopic gestation in the patient with a history of infertility or the timing of subsequent treatments.

Abstract

To evaluate the cost effectiveness of laparoscopy for unexplained infertility.We performed a cost-effectiveness analysis using a computer-generated decision analysis tree. Data used to construct the mathematical model were extracted from the literature or obtained from our practice. We compared outcomes following four treatment strategies: [1] no treatment, [2] standard infertility treatment algorithm (SITA), [3] laparoscopy with expectant management (LSC/EM), and [4] laparoscopy with infertility therapy (LSC/IT). The incremental cost-effectiveness ratio (ICER) was calculated, and one-way sensitivity analyses assessed the impact of varying base-case estimates.Academic in vitro fertilization practice.Computer-simulated patients assigned to one of four treatments.Fertility treatment or laparoscopy.Incremental cost-effectiveness ratios.Using base-case assumptions, LSC/EM was preferred (ICER =$128,400 per live-birth in U.S. dollars). Changing the following did not alter results: rates and costs of multiple gestations, penalty for high-order multiples, infertility treatment costs, and endometriosis prevalence. Outcomes were most affected by patient dropout from infertility treatments-SITA was preferred when dropout was less than 9% per cycle. Less important factors included surgical costs, acceptability of twins, and the effects of untreated endometriosis on fecundity.Laparoscopy is cost effective in the initial management of young women with infertility, particularly when infertility treatment dropout rates exceed 9% per cycle.

Abstract

To investigate the hypothesis that surgical treatment of endometriosis in infertile patients may improve pregnancy rates by improving embryo quality.We conducted a retrospective evaluation of 30 infertile patients treated with in vitro fertilization (IVF) before and after surgery for endometriosis. Patients served as their own controls and only cycles with similar stimulation protocols were compared.Using standard visual evaluation, embryo quality on day 3 was similar before and after surgical treatment of endometriosis. Fifty seven percent of patients had stage I-II endometriosis and 43% had stage III-IV disease. No patients had a live birth after the first IVF cycle and 43% of patients had a live birth with the IVF cycle after surgery.Surgical treatment of endometriosis does not alter embryo quality in patients with infertility treated with IVF.

Abstract

To determine whether an elevated basal FSH concentration is an independent predictor of fetal aneuploidy, as measured in spontaneous abortions (SAB).Retrospective study.Academic reproductive endocrinology and infertility center.All women with karyotypes of chorionic villi isolated from first trimester spontaneous miscarriages at the time of dilation and curettage from 1999 to 2006. The highest basal serum FSH level in the year preceding dilation and curettage was recorded.Monitoring of early pregnancy.Fetal karyotype.A total of 177 spontaneous miscarriages with karyotypes (70 euploid and 107 aneuploid) were identified, of which 53% were conceived by IVF. The aneuploid cohort consisted of trisomic (87%), teraploid (9.3%), and monosomic (3.7%) gestations. Using logistic regression analysis, basal FSH was not found to be independently predictive of an aneuploid gestation in our data set.Our data do not support the hypothesis that an elevated basal FSH concentration is associated with an increase in fetal aneuploidy. Our findings suggest that the association between diminished ovarian reserve and SAB may result from nonkaryotypic factors.

Abstract

Hundreds of thousands of human embryos are cultured yearly at in vitro fertilization (IVF) centers worldwide, yet the vast majority fail to develop in culture or following transfer to the uterus. However, human embryo phenotypes have not been formally defined, and current criteria for embryo transfer largely focus on characteristics of individual embryos. We hypothesized that embryo cohort-specific variables describing sibling embryos as a group may predict developmental competence as measured by IVF cycle outcomes and serve to define human embryo phenotypes.We retrieved data for all 1117 IVF cycles performed in 2005 at Stanford University Medical Center, and further analyzed clinical data from the 665 fresh IVF, non-donor cycles and their associated 4144 embryos. Thirty variables representing patient characteristics, clinical diagnoses, treatment protocol, and embryo parameters were analyzed in an unbiased manner by regression tree models, based on dichotomous pregnancy outcomes defined by positive serum beta-human chorionic gonadotropin (beta-hCG). IVF cycle outcomes were most accurately predicted at approximately 70% by four non-redundant, embryo cohort-specific variables that, remarkably, were more informative than any measures of individual, transferred embryos: Total number of embryos, number of 8-cell embryos, rate (percentage) of cleavage arrest in the cohort and day 3 follicle stimulating hormone (FSH) level. While three of these variables captured the effects of other significant variables, only the rate of cleavage arrest was independent of any known variables.Our findings support defining human embryo phenotypes by non-redundant, prognostic variables that are specific to sibling embryos in a cohort.

Abstract

To evaluate obstetric complications in women who conceived through donated oocytes compared with women who conceived through assisted reproduction using autologous oocytes.Retrospective cohort analysis.Stanford Hospital and Clinics and Lucille Packard Children's hospital, both tertiary referral centers.A cohort of 71 oocyte recipients who underwent in vitro fertilization (IVF) were compared to all women over 38 years who conceived through IVF with autologous oocytes (n = 108) between January 1, 2001, and December 31, 2005, at Stanford University and subsequently delivered infants at Lucille Packard Children's Hospital.Assisted reproductive technology with donor oocytes.Obstetric charts of the donor-oocyte recipients were compared for all women over 38 years old who had conceived through IVF with autologous oocytes at the same center (n = 108) and delivered at the same hospital during the same time period. Perinatal complications including preeclampsia, diabetes, preterm labor, preterm premature rupture of membranes and placental abnormalities, mode of delivery, presentation, Apgar scores, gestational age at delivery, and weight were compared between the groups.Oocyte recipients and autologous oocyte controls had similar rates of complications of prematurity, hypertensive disorders of pregnancy, gestational diabetes, and placental abnormalities. Infant birth weights and gestational age at time of delivery were similar between the two groups.This study suggests that women undergoing IVF with donor oocytes are not at increased risk for complications during pregnancy or at increased immediate neonatal complications compared with women of advanced maternal age undergoing IVF with autologous oocytes.

Abstract

To evaluate the frequency of specific aneuploidies in miscarriages in an infertility practice and calculate the potential sensitivities of the different aneuploidy screening options for preimplantation genetic diagnosis (PGD) in this setting.Retrospective analysis.Academic reproductive endocrinology and infertility practice.Women with miscarriages that had karyotype analysis on products of conception.None.Karyotype of spontaneous abortions compared with commercially available PGD options.Of the 273 karyotypes analyzed, 177 (64.8%) were abnormal. The average age of the patients was 37 +/- 4.5 years. Using a limited five-probe panel, 54 of the 177 (31%) abnormal karyotypes would have been detected. In contrast, an extended PGD panel (using 9, 10, or 12 chromosome probes) would have detected 127, 131, and 140 of 177 abnormalities, 72%, 74%, and 79% respectively. The difference between the limited (5-probe) and extended (9-, 10-, and 12-probe) panels was statistically significant. There was not a statistically significant difference among the extended panels.Most of the abnormalities seen in miscarriages are detectable by PGD with extended panels. A significantly higher percentage of these abnormalities could be detected by screening for 9, 10, or 12 chromosomes compared with only 5.

Abstract

To report the case of a patient undergoing in vitro fertilization (IVF) in which a non-pronuclear (0PN) oocyte resulted in a normal pregnancy.A 36-year-old woman underwent an IVF-embryo transfer treatment cycle.Four oocytes were retrieved for insemination by IVF. Examination for fertilization revealed two polypronuclearpolygynic and two non-pronuclear oocytes. The non-pronuclear oocytes were observed further for development. One embryo developed from the non-pronuclear cohort and was transferred at the 8-cell stage on day 3. Subsequently, a pregnancy developed, and resulted in the delivery of a healthy term infant.Non-pronuclear oocytes may represent a source of developmentally competent embryos, and further observation of this cohort should be considered, particularly in situations involving a low yield of oocytes at retrieval.

Abstract

A retrospective review of all patients older than 35 who underwent elective single blastocyst transfer was performed. Twenty-three of the 45 patients (51.1%) have an ongoing pregnancy or liveborn delivery, with a mean age of 37.3 years, demonstrating a clear role for elective single transfer in this relatively older IVF population.

Abstract

The objective of this study is to determine the rate of abnormalities detected by cytogenetic testing of first trimester miscarriages, in patients with and without an embryonic pole seen on ultrasound.A retrospective study of 272 D&Cs for missed abortions in an academic infertility practice from 1999 to 2006. Karyotype results were compared with transvaginal ultrasound findings. Chi-squared analysis was used with a P < 0.05 for significance.There was a high rate of abnormal karyotypes in all miscarriages (65%). Rates of abnormal karyotypes were 58% and 68% in cases with anembryonic gestations and those with a fetal pole seen, respectively (P > 0.05).The high rate of abnormalities detected in both groups suggests that useful results can be obtained from chromosomal testing of the POC regardless of ultrasound findings. Further studies on the prognostic value and cost effectiveness of chromosomal testing are needed.

Abstract

To compare pregnancy rates (PR) for letrozole and gonadotropins in individuals who failed to conceive with clomiphene citrate (CC).Retrospective cohort study.University reproductive center.Individuals treated with letrozole or gonadotropins who failed to conceive with CC.Controlled ovarian hyperstimulation (COH), transvaginal ultrasound, ovulation induction, IUI.Pregnancy rates per cycle.Among patients who failed to conceive with at least three cycles of CC, gonadotropins had a higher PR per cycle than letrozole. Among individuals who failed to conceive with less than three cycles of CC and whose medications were changed because of thin uterine lining or intolerable side effects, average PR per cycle for letrozole and gonadotropin treatments were equivalent. All patients conceived within three stimulation cycles with either gonadotropins or letrozole.In patients who failed to conceive with CC, gonadotropins have higher PR for ovulation induction than letrozole. However, PR were high enough with letrozole to justify its use in this population of patients. Letrozole and gonadotropins should not be used for more than three cycles without a conception.

Abstract

Infertility is a concern to young women diagnosed with breast cancer. Advances in fertility technology have made it possible to bank fertilized embryos.Twenty-three women, ages 27 to 40 years, underwent stimulation/oocyte retrieval before the start of adjuvant therapies. Time intervals between retrieval and therapeutic procedures were analyzed.The average stimulation to egg retrieval was 11.5 days (range 9-20 d). The average time interval from first evaluation to oocyte retrieval was 33.3 days (range 10-65 d). Overall, the mean time from definitive surgery to initiation of chemotherapy was 46.8 days (n = 20). For 6 patients referred by surgeons, the mean time from fertility consult to retrieval was 48.8 days (range 16-118 d), and from definitive surgery to initiation of chemotherapy was 45 days (range 15-93 d).Egg retrieval cryopreservation can be integrated with breast cancer work-up and surgical procedures. Early referrals to a fertility specialist by surgeons will help patients' safeguard future childbearing.

Abstract

To evaluate obstetric complications in women conceiving with donated oocytes as compared to controls of advanced maternal age.We compared the obstetric outcomes of a cohort of 69 women who conceived through oocyte donation to all women over 38 years old (n = 681) who delivered at the same hospital in the same period. We first compared obstetric complications and outcomes in the entire cohort. Additional comparisons were made while controlling for multiple covariates: maternal and fetal complications, mode of delivery, estimated gestational age and infant weight at delivery.Women who conceived with donor oocytes were older than controls. In the cohort, oocyte recipients were at increased risk for several obstetric complications. However, when controlling for age and multiple gestations, only preterm labor, preeclampsia and protracted labor were increased in oocyte recipients.Women who conceive with donor oocytes might be at increased risk of complications during pregnancy. When age and multiple gestations are accounted for, these patients remain at risk for preterm labor, preeclampsia and protracted labor requiring cesarean delivery.

Abstract

The purpose of our study is to compare the occurrence of monozygotic twinning (MZT) from blastocyst transfer (BT) in our program between an earlier and more recent time period.Retrospective.Academic IVF practice.All pregnancies conceived between March 2002 and December 2005 (N = 932) in our program were compared to pregnancies conceived before March 2002 (N = 554), which were the subject of a previous study.None.The incidence of MZT with day 3 embryo transfer and BT were compared between the study and control groups.During the study period, the rate of MZT was not significantly different for BT at 2.3% (9/385) compared to day 3 embryo transfer at 1.8% (10/547). This rate of 2.3% for BT was significantly lower than the rate of 5.6% (11/197) reported at our institution for BT before March 2002.Our study suggests that the risk of MZT with BT is significantly lower in the more recent time period and is in the range of what is seen with cleavage stage transfer. It is likely that improvements in culture systems as experience is gained with BT played a role.

Abstract

A 34-year-old nulligravid woman experienced hemorrhage after each of 2 oocyte retrievals. Initial coagulopathy screening was negative. Treatments used during in vitro fertilization likely interfered with assay performance. Reevaluation remote from medications confirmed the diagnosis of von Willebrand disease. Treatments used during in vitro fertilization may increase bleeding risk and confound coagulopathy evaluation.

Abstract

We compared the effects of two standard oxygen concentrations, physiological (5% O(2), 5% CO(2), and 90% N(2)) and atmospheric (5% CO(2) with the balance as air), on fertilization, embryo development, and pregnancy rate in 106 patients undergoing IVF, excluding donor oocyte cycles and preimplantation genetic diagnosis cycles. The differences in oxygen concentration did not significantly affect fertilization rate, blastocyst formation, or pregnancy rate, but there was a significant difference in mean embryo score between physiological and atmospheric groups on day 3.

Abstract

To determine the impact of nutritional supplementation on female fertility.A double blind, placebo-controlled study of the effects of FertilityBlend for Women, a proprietary nutritional supplement containing chasteberry, green tea, L-arginine, vitamins (including folate) and minerals, on progesterone level, basal body temperature, menstrual cycle length, pregnancy rate and side-effects.Ninety-three (93) women, aged 24-42 years, who had tried unsuccessfully to conceive for six to 36 months, completed the study. After three months, the FertilityBlend (FB) group (N = 53) demonstrated a trend toward increased mean mid-luteal progesterone (P(ml)), but among women with basal pretreatment P(ml) < 9 ng/ml, the increase in progesterone was highly significant. The average number of days with luteal-phase basal temperatures over 98 degrees F increased significantly in the FB group. Both short and long cycles (< 27 days or > 32 days pretreatment) were normalized in the FB group. The placebo group (N = 40) did not show any significant changes in these parameters. After three months, 14 of the 53 women in the FB group were pregnant (26%) compared to four of the 40 women in the placebo group (10%; p = 0.01). Three additional women conceived after six months on FB (32%). No significant side-effects were noted.Nutritional supplements could provide an alternative or adjunct to conventional fertility therapies.

Abstract

To evaluate the effect of oral contraceptive pill (OCP) pretreatment in patients undergoing IVF cycles with an antagonist.In this retrospective study, 194 cycles of women with diminished ovarian reserve undergoing IVF with a protocol using GnRH antagonists were evaluated. Oral contraceptive pretreatment was used in 146 cycles.Pregnancy rates were the same in both groups. Patients using OCPs required more gonadotropins (5,890 IU) compared to patients not undergoing OCP pretreatment (4,410 IU).Pregnancy outcomes were the same whether or not OCP pretreatment was implemented in poor responders using an antagonist protocol. While OCP pretreatment may help with scheduling flexibility, the higher dose of gonadotropins needed for ovarian stimulation should be considered.

Abstract

To review options for fertility preservation in women with gynecologic cancers.Literature review.We discuss the data regarding cancer treatment and fertility outcomes and current controversies for women with gynecologic cancers.Gynecologic cancers represent 12%-15% of cancers affecting women, and 21% of these are diagnosed in women of reproductive age. Current advances in our understanding of these diseases, along with improved multimodality treatment, allow for consideration of fertility options. For some women with gynecologic cancers, fertility-sparing treatment might be appropriate.

Abstract

Many will agree that the use of laparoscopy to diagnose and potientially treat endometriosis in patients who suffer from infertility has been superseded by IVF and sometimes oocyte donation, especially in older patients. The findings of our study add another dimension to management of endometriosis in the setting of infertility and emphasize the importance of keeping laparoscopy in the infertility management equation.

Abstract

To describe a case of embryo cryopreservation before hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer.Case report.University and community service.An infertile woman with endometrial biopsy demonstrating grade II/III moderately differentiated endometrial adenocarcinoma.A Progestasert intrauterine device (IUD) was inserted into the uterine cavity to potentially reduce tumor proliferation during the stimulation cycle followed by oocyte retrieval and cryopreservation of 14 embryos.Pregnancy.Successful pregnancy in a gestational carrier.Embryo cryopreservation and use of a gestational carrier may offer a fertility option for patients with endometrial malignancies without substantially delaying treatment.

Abstract

To report on a patient with a monochorionic triamnionic triplet pregnancy after IVF with donor oocytes.Case report.Academic tertiary care hospital.A 42-year-old woman who underwent IVF with donor oocytes.After failed IVF attempts, the patient chose to undergo treatment with donor oocytes. Her 23-year-old oocyte donor underwent standard controlled ovarian hyperstimulation. Retrieved oocytes were fertilized in vitro, and two embryos were transferred at the blastocyst stage.Intrauterine pregnancy with single gestational sac and three fetal poles with cardiac activity.After extensive counseling with perinatologists about pregnancy complications, the patient elected to terminate at 10 weeks of gestation.Several processes have been suggested to explain the increase in monozygotic twinning after IVF. These factors include advanced maternal age, superovulation, manipulation of the zona pellucida, and prolonged culture. It is possible that other factors may also play a role, especially in high-order monozygotic multiple pregnancies. All patients should be informed of the potential risk of a high-order multiple pregnancy after IVF, even when only one or two embryos are transferred.

Abstract

To assess the accuracy of drug self-reporting in oocyte donors.Retrospective chart review of donors at Stanford University.7% of the donor population had a significant positive urine toxicology screen.Donors may not fully disclose details of drug use, so urine toxicology screening should be considered in this patient population.

Abstract

To compare the efficacy and safety of three different ratios of human-derived follicle-stimulating hormone/human menopausal gonadotropin (human-derived FSH:hMG, Bravelle and Repronex) mixed together in the same syringe and administered subcutaneously once daily, to in vitro fertilization (IVF) patients <34 years or 34 to 40 years of age.Two randomized, prospective, age stratified, IVF studies.Twenty-one academic and private clinics with experience in IVF/embryo transfer (ET).Infertile premenopausal women undergoing IVF-ET.Pituitary suppression with leuprolide acetate, randomization to one of three treatment groups, followed by gonadotropin stimulation (GS) for up to 15 days. The human-derived FSH:hMG ratios were the following: Group 1, a 1:1 ratio throughout; Group 2, a 3:0 ratio that was changed to 1:1 after GS day 5; Group 3, a 2:1 ratio that was increased to 3:1, 4:1, or 5:1 after GS day 5, as needed.Mean number of oocytes retrieved; peak estradiol levels; dose and duration of stimulation; implantation rates; adverse events; injection site pain; and pregnancy and live birth rates.Overall, women <34 years had higher E(2) levels, more oocytes retrieved, and improved implantation and live birth rates compared with women 34 to 40 years old. Nonetheless, each ratio of human-derived FSH:hMG produced comparable implantation rates, and continuing pregnancy and take-home baby rates.All three ratios of human-derived FSH:hMG in both age groups produced comparable pregnancy and live birth rates with similar safety results.

Abstract

This report describes our initial experience with elective single blastocyst transfer in 19 patients who had a mean age of 36.3 +/- 2.4 years. The ongoing pregnancy rate, 53% after the fresh embryo transfer and 68% when thaw cycles are included, suggests that single blastocyst transfer has a place in this relatively older patient population.

Abstract

To reassess the use of TEST-yolk buffer (TYB) in an in vitro fertilization (IVF) program by comparing fertilization rates achieved in a glucose-free cleavage medium by the standard IVF preparation of sperm versus a 2-h, room temperature incubation of sperm in TYB.Oocytes collected for IVF were randomly split into two groups and inseminated with either TYB-treated sperm or IVF-prepared sperm.Stanford Reproductive Endocrinology and Infertility Center.Fifty couples undergoing IVF with at least 10 mature oocytes.Fertilization rates in vitro.Fertilization rates were significantly higher (p = 0.015) with TYB treatment. The average 2PN fertilization rate was 49.6% (188/379) for the IVF group and 57.4% (221/385) in the IVF with TYB group.A 2-h, room temperature incubation of sperm in TYB produces significantly higher 2PN fertilization rates as compared to standard IVF preparation of sperm in a current generation cleavage medium.

Abstract

To determine the impact of nutritional supplementation on optimization of reproductive health in women.A double-blind, placebo-controlled pilot study was initiated to determine the effects of FertilityBlend (Daily Wellness Co., Sunnyvale, California), a proprietary nutritional supplement containing chasteberry and green tea extracts, L-arginine, vitamins (including folate) and minerals. Changes in progesterone level, basal body temperature, menstrual cycle, pregnancy rate and side effects were monitored.Thirty women aged 24-46 years who had tried unsuccessfully to conceive for 6-36 months completed the study. After 3 months, the supplement group (n = 15) demonstrated a trend toward an increase in mean midluteal phase progesterone level (from 8.2 to 12.8 ng/mL, P = .08) and a significant increase in the average number of days in the cycle with basal temperatures >37 degrees C during the luteal phase (6.8-9.7 days, P = .04). The placebo group (n = 15) did not show any notable changes after treatment in any of the parameters studied. After 5 months, 5 of the 15 women in the supplement group were pregnant (33%), and none of the 15 women in the placebo group were (P

Abstract

This study evaluated the first multiple-use pen device for the self-administration of recombinant FSH. The pen device is used for the subcutaneous injection of a pre-mixed ready-to-use solution of follitropin beta from a multiple-dose cartridge, and has flexible dosing capabilities. In the ease-of-use questionnaire, 90% of subjects rated the overall experience of self-injecting follitropin beta using the pen device as 'very good' (on day 6). The comprehension questionnaire revealed that prior to the first injection and during the second injection, the follitropin beta cartridge was properly loaded into the pen device by 96.7 and 100% of the subjects respectively. The questionnaire also showed that the correct dose was selected and self-administered by 98.3 and 100% of the subjects respectively. Biochemical and ongoing pregnancy rates per attempt were 56.7 and 45.0% respectively. The pen device is safe, effective, and easy to use for self-administering recombinant FSH during ovarian stimulation.

Abstract

To evaluate the sex ratio in births conceived with blastocyst transfer compared to day 3-ET.A retrospective analysis of IVF patients who became pregnant after blastocyst or cleavage stage transfer at Stanford University Hospital and a literature review were performed.In the day 3-ET group, the male-to-female (M/F) ratio was 157/139 (53%/47%) compared to 97/66 (59.5%/40.5%) in the blastocyst group (P = 0.18). Similar trends have been found in individual studies in the literature but reached statistical significance in only one out of six reports reviewed. The combined data from our study and the literature show a male-to-female ratio of 797/594 (57.3%/42.7%) in blastocyst transfer compared to 977/932 (51.2%/48.8%) in day 3-ET (P = 0.001).Although individual studies may lack power to show an altered sex ratio with blastocyst transfer, the combined data presented in this report do suggest that the M/F ratio is higher with blastocyst transfer compared to cleavage stage transfer.

Abstract

To describe a case of primary infertility associated with oocytes having one pronucleus before fertilization on repeated IVF attempts.Case report.A university-based assisted reproduction unit.A 30-year-old woman with primary infertility and oocytes containing one pronucleus before fertilization.Oocyte donation.Pregnancy.Conceived triplets after transfer of three embryos using donor oocytes.This patient's infertility was likely associated with an oocyte abnormality, as evidenced by the premature formation of one pronucleus before fertilization. In the future, more studies on the appearance of a single pronucleus before fertilization will be needed to determine its overall significance on fertility.

Abstract

To investigate whether ICSI (intracytoplasmic sperm injection) results in decreased blastocyst formation and pregnancy compared to IVF (in vitro fertilization).We performed a retrospective analysis of blastocyst transfer (BT) offered routinely to patients under age 40 with > or = three 8-cell embryos on day 3 and compared IVF to ICSI cycles. Sequential media were used with P1 until day 3, then Blastocyst Medium until day 5/6.There were 131 IVF and 75 ICSI cycles. There was no difference in age, number of oocytes, zygotes, 8-cell embryos, blastocysts on days 5 and 6, or embryos transferred. Progression to blastocyst was similar (78% for IVF and 73% for ICSI) as was the viable pregnancy rate (51.4% for IVF and 55% for ICSI). No cycles failed to form blastocysts.The progression to blastocyst and the likelihood of conceiving a viable pregnancy were unaltered by ICSI. Thus it seems appropriate for programs to offer BT to patients undergoing ICSI using the same inclusion criteria applied to their IVF patients.

Abstract

To evaluate the incidence of monozygotic twinning (MZT) in pregnancies conceived after blastocyst transfer compared to cleavage-stage transfer.Retrospective study.University IVF program.All IVF patients with viable pregnancies conceived during a 4-year period.Blastocyst transfer or day 3 ET.Incidence of MZT assessed by transvaginal ultrasound.There were 11 incidences of MZT in 197 viable pregnancies (5.6%) with blastocyst transfer compared to 7 of 357 viable pregnancies (2%) with day 3 ET. In 10 of 18 pregnancies, MZT was observed in the setting of a higher order multiple gestation (6 of 11 for blastocyst transfer and 4 of 7 for day 3 ET). In the day 3 ET group, assisted hatching or intracytoplasmic sperm injection (ICSI) did not increase MZT (4 of 213, 1.9%) compared to cycles without zona breaching (3 of 144, 2.1%). Similarly, in the blastocyst-transfer group, ICSI did not increase the incidence of MZT (4 of 74, 5.5% for ICSI and 7 of 123, 5.7% for non-ICSI IVF).Compared to day 3 ET, blastocyst transfer appears to significantly increase the incidence of gestations with MZT. This information should be taken into account when counseling patients about the pros and cons of extended culture.

Abstract

To assess the accuracy of day 3 morphologic criteria in identifying the best embryos.Prospective observational study.University IVF program.One hundred cycles in women desiring blastocyst transfer who had > or =3 eight-cell embryos on day 3.On day 3, the embryologist chose the two embryos that would have been transferred that day. On day 5, embryos were examined to determine the best and second-best blastocysts.Accuracy of day 3 picks as measured in culture on day 5, outcome of nontransferred picks, and cryopreservation rate.All cycles reached the blastocyst stage and 73% had cryopreservation. The mean number of blastocysts was 4.8 (3.2 on day 5 and 1.6 on day 6). Neither pick was chosen in 39% of cycles; one pick was transferred in 38%; and both picks were transferred in 23%. Of 116 nontransferred picks, 51 were frozen and 65 arrested, with both picks arresting in 9 cycles. The single best blastocyst was chosen from the picks in 39% of cycles.Morphologic criteria for cleavage-stage embryo selection may fall short when the transfer is limited to two embryos. Culture to blastocyst is warranted in this population to avoid high-order multiples and still be able to choose the two embryos with the highest implantation potential.

FIRST REPORT OF A VAGINAL FOREIGN-BODY PERFORATING INTO THE RETROPERITONEUMAMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGYOHANLAN, K. A., Westphal, L. M.1995; 173 (3): 962-964

Abstract

Pelvic examination of a 19-year-old woman with recurrent pain after multiple laparotomies revealed a 4.0 cm paracervical fibroepithelial polyp and tender fullness in the left pelvis. Abdominal exploration had normal findings, but exploration of the retroperitoneum revealed an encysted bottle cap that had eroded through the vaginal wall years before.

Abstract

Transforming growth factor-alpha (TGF-alpha) has been shown to be a potent stimulant of oocyte maturation and embryonic development. The role of maternal growth factors and their mechanism of action in early mammalian development is not well understood.In this study, the presence of TGF-alpha and epidermal growth factor receptor (EGF-R) in human cumulus cells and fallopian tubes was investigated by immunocytochemical techniques.The fallopian tube showed intense staining for TGF-alpha in the apical region of the epithelial cells, and the cumulus cells showed intense staining for EGF-R on cell membranes.The presence of TGF-alpha in the fallopian tube epithelium and its receptor on cumulus cells suggest a paracrine mechanism between maternal growth factors and the developing embryo.

Abstract

Spermatozoa change their movement characteristics in response to different environmental conditions. To investigate the relative force of spermatozoa exhibiting different motility patterns, a laser optical trap was used. A laser beam at 760 nm was directed through a microscope objective and focused above the spermatozoa to create a three-dimensional optical trap. Spermatozoa were trapped at 300 mW, and laser power was reduced until spermatozoa could escape. The force generated by the flagellar movement was proportional to the laser power at which the spermatozoa escaped from the trap. Three motility patterns were studied: linear, hyperactivated, and cumulus-related. Mean escape power for spermatozoa displaying linear motility was 59.5 +/- 43 mW, for hyperactivated motility 122.3 +/- 67 mW (P < 0.0001) and for cumulus-related motility 200.6 +/- 44.2 mW (P < 0.0001). In this study, we showed that human spermatozoa generated more relative force upon exposure to the cumulus mass. The combination of small-amplitude lateral head displacement and higher relative force may produce a 'drilling' effect which is synergistic with the enzymatic digestion of the cumulus matrix during the fertilization process.

Abstract

To investigate the messenger ribonucleic acid (mRNA) expression of interleukin-1 (IL-1) type I receptor in the endometrial tissue of normal patients during the menstrual cycle.Prospective longitudinal study.Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, California.Twenty fertile women between 19 and 41 years of age underwent hysterectomy for benign reasons (n = 9) and laparoscopy for tubal ligation (n = 11). In all cases, endometriosis was not visualized.Endometrial biopsy using the Novak curette was obtained at the time of surgery.Total RNA extracted from unfractioned endometrial tissue was analyzed on Northern blots by using specific complementary deoxyribonucleic acid probes.We found IL-1 type I receptor mRNA expression in endometrial tissue throughout the entire menstrual cycle. However, IL-1 type I receptor mRNA levels were significantly higher during both early and late luteal phases than follicular and midluteal phases.Our results demonstrate the presence of the IL-1 system in the human endometrium and that the receptor is regulated throughout the menstrual cycle with a 4.1-fold increased expression of the IL-1 receptor gene in the early luteal phase compared with preovulatory endometrium.

Abstract

Spermatozoa from long-term vasectomized mice have greatly reduced fertilizing ability in vivo and in vitro, which makes this a useful animal model for male factor infertility. The purpose of this study was to evaluate the 308 nm XeCl excimer laser for opening the zona pellucida to enhance the fertilization rate with spermatozoa from vasectomized males. Inseminating zona-intact (control) oocytes with 5 x 10(6) spermatozoa/ml resulted in only 6% fertilization and 33.3% development to the blastocyst stage; zona-opened oocytes showed significant improvement with 31.5% fertilization, 90% cleavage to the 2-cell stage, and 72.2% blastocyst formation. Out of the 130 oocytes in the experimental group, zona ablation was performed successfully on 127 and only three were damaged. These results suggest that laser micromanipulation for assisted fertilization potentially offers a simplified and precise method for mechanical zona cutting.

Abstract

To improve the assessment of sperm penetration during the hamster penetration assay, we compared the Hoechst 33342 and 33258 DNA-specific fluorescent stains with the standard acetolacmoid stain. The fluorescence stains produced distinct staining of the DNA within the egg cytoplasm and nucleus, and this allowed for accurate and fast assessment of sperm penetration.

Abstract

Propofol is an intravenous anesthetic currently available for clinical investigative use. The intraoperative and postoperative effects of propofol were compared to methohexital when used as an adjuvant to nitrous oxide for outpatient anesthesia. Sixty healthy young women were randomly assigned to receive either methohexital, 1.5 mg/kg intravenously (IV), or propofol, 2.5 mg/kg IV, for induction of anesthesia. Both drugs produced transient cardiovascular and respiratory depression after induction. Maintenance of anesthesia consisted of either methohexital, 6 +/- 2 mg/min, or propofol, 7 +/- 2 mg/min (mean +/- SD) by continuous infusion in combination with nitrous oxide, 70% in oxygen. Use of a propofol infusion was associated with lower blood pressures and heart rates during maintenance. Propofol was associated with fewer side effects (e.g., hiccoughing, nausea, and vomiting) intra- and postoperatively. Recovery times for awakening, orientation, and ambulation were consistently shorter with propofol. We conclude that propofol is a useful alternative to methohexital for induction and maintenance of outpatient anesthesia.

Abstract

Isolated oocytes from 30 unstimulated Xenopus laevis females required from 2.50 +/- 0.13 to 14.59 +/- 0.77 hr after progesterone exposure for the first 50% of each group to complete meiotic maturation. Injecting 8 females with an amount of hCG not causing ovulation (25 micrograms, 96 IU) lowered oocyte maturation times by 45-83%. An enzyme-linked immunosorbent assay (ELISA) of the blood of 18 unstimulated animals found a constituent which bound to anti-hCG in amounts (equivalent to 0-1.03 micrograms/ml hCG) that had a direct relationship to the rates of GVBD in oocytes. Preincubation of manually isolated follicles in 0.25-1.25 micrograms/ml hCG shortens oocyte maturation times by 18-50% in a direct, nonlinear fashion and this priming effect is reversed when hCG is withdrawn. The action of gonadotropins in facilitating germinal vesicle breakdown (GVBD) mimics the previously reported priming effect produced by preincubation of oocytes in subthreshold levels of progesterone. Evidence suggests that individual variation in the time course of progesterone-induced meiotic maturation of amphibian oocytes is the result of priming differences caused by the action on follicle cells of fluctuating blood levels of an LH-like hormone.